Enteric phageome alternations in Type 2 diabetes disease

Abstract

Background Type 2 diabetes (T2D) is a complex metabolic disease and has been proved to involve in the alternation of the gut microbiota. The previous studies primarily focused on the changes in bacteriome while ignoring the phage community composition. The extracellular phages could lyse the host bacteria, and thus influence the microbiota through the positive or negative interactions with bacteria. We investigated the change of extracellular phageome and explored its role in T2D pathogenesis.Results We used a sequencing-based approach to identify the bacteriophage after isolation of VLPs from the fecal samples. We identified 330 phages according to the predicted host bacteria. The phageome characteristics were highly diverse among individuals. In the T2D group, the intestinal phage population is altered and the abundance of 7 identified phages specific to Enterobacteriaceae hosts were found increased markedly. Additionally, the abundance of Enterobacteriaceae bacteria in gut was significantly increased and the systemic LPS elevation was observed in T2D group. Several phage consortia were found to have significant correlations with T2D disease indicators.Conclusions The alteration of bacteriophages predicted to infect Enterobacteriaceae in the gut was observed in this study, which was expected to be a new source of systemic LPS in T2D patients, and may contribute to the pathogenesis of the disease. The data present in this study revealed the similar variation trend in enteric bacteriome and the correlated bacteriophages, which is likely to shed considerable light on overall understanding the interactions between microbiome and metabolic diseases.

Enteric Phageome Alterations in Patients With Type 2 Diabetes

“…This manuscript has been released as a pre-print at Research Square, https://www. researchsquare.com/article/rs-7995/v1 (Chen et al, 2019).…”

The Human Gut Phageome: Identification and Roles in the Diseases

“…As a result, it is possible that B. Dorei might alter the autoimmunity of islet cells via gene manipulation [62]. Similarly, the gut phages of T2D patients carried a large number of genes that silently contributed to the pathogenesis of the human disease [42,63,64]. A bioinformatics study based on metagenomic sequencing and intestinal phage types in stool samples from normal and T2DM individuals identified that the number of phages, particularly the T2DM-specific phage 7 pOTU, in the intestinal tract of diabetic patients was significantly increased [28].…”

“…The results of their study revealed that there was not only an increase in Enterobacteriaceae bacteria but also a significant shift in intestinal phage populations, such that abundances of 7 distinct phages were detected to be elevated specifically associated with Enterobacteriaceae hosts as contributing factors to T2D pathogenesis and development. Furthermore, tissue samples from T2D patients have shown an increase in podoviridae, a bacteriophage that infects E.coli and Clostridium and reproduces alongside its host bacteria as a part of the disease [64]. As the first strategy to prevent the harmful effects of gut microbiota on diabetic patients, fecal virome transplantation (FVT) has been shown to alleviate obesity and type 2 diabetes in mice, by altering the bacterial and viral components of the intestinal microbiota.…”

“…2) In the intestinal tract of diabetic patients, 7 pOTU, podoviridae, and CrAssphage were significantly increased [21,64,65] Inflammatory bowel disease 1) Both CD and UC patients exhibit dysbiosis of gut bacteria including an expanded population of potentially pathogenic proteobacteria (e.g., E. coli and Fusobacteria) and a reduced population of potentially protective Firmicutes (e.g., Faecalibacterium prausnitzii, Rumininococci, and Clostridium clusters IV and XIVa.…”